tbuckley/cabot-search huggingface dataset:
OP0144 ASSOCIATION OF HEALTHY LIFESTYLES WITH ALL-CAUSE AND CAUSE-SPECIFIC MORTALITY AMONG INDIVIDUALS WITH OSTEOARTHRITIS: A PROSPECTIVE COHORT STUDY OF THE UK BIOBANK
Authors: T. Fan, M. Zeng, S. Chen, H. Yang, X. Fang, Y. Zhang, P. Cao, Z. Wang, Y. Zhang, D. Hunter, Q. Yang, L. Lin, H. Guo, Y. LI, S. N. Fu, C. Ding, Z. Zhu
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Healthy lifestyles are thought to reduce the risk of multiple causes of mortality in general population. However, whether and to what kind of healthy lifestyles could offset the risk of multiple causes of mortality in patients with osteoarthritis (OA) are unknown. <h3>Objectives</h3> This study aimed to investigate the association of both individual and combined healthy lifestyle factors with the risk of all-cause and cause-specific mortality among participants with OA. <h3>Methods</h3> 104,142 OA participants were included from the UK Biobank (mean age 60±7.0). A summed healthy lifestyle score was constructed using body mass index (BMI) and self-reported diet, sleep duration, physical activity, sedentary time, social connection, smoking and alcohol drinking. Restricted cubic spline (RCS) and Cox proportional hazards models were used to examine the associations of individual factors and a combined healthy lifestyle score with the risk of all-cause and cause-specific mortality. <h3>Results</h3> During a median follow-up of 12.7 years, 9915 deaths after the first two years follow-up were recorded. Using RCS models, sleep duration had a U-shaped (with a nadir at 7 h/day), moderate physical activity (MPA) had an L-shaped (with a turning point at 550 min/week), while BMI and vigorous physical activity (VPA) had J-shaped (with turning points at 28 kg/m<sup>2</sup> and 240 min/week respectively) associations with all-cause mortality. In multivariable Cox models, each lifestyle factor was significantly associated with all-cause mortality, and hazard ratios (95%CI) associated with newly constructed healthy lifestyle score (scoring 7-8 vs. 0-2) were 0.29 (0.25-0.35) for all-cause mortality, 0.40 (0.32-0.50) for cancer-cause mortality, 0.22 (0.17-0.30) for cardiovascular disease mortality, 0.27 (0.16-0.48) for digestive-cause mortality and 0.18 (0.12-0.25) for respiratory mortality. <h3>Conclusion</h3> This study introduced a healthy lifestyle pattern that could significantly reduce the risk of all-cause and cause-specific mortalities in OA patients. <h3>Acknowledgements</h3> We thank all the participants and staff in the UK Biobank. <h3>Disclosure of Interests</h3> None Declared.
OP0132 CANCERS AND CARDIOVASCULAR DISEASES IN PATIENTS WITH SEROPOSITIVE RHEUMATOID ARTHRITIS TREATED WITH JAK INHIBITORS AND BIOLOGICS
Authors: S. S. Ahn, M. Han, I. Jung, H. W. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Janus kinase inhibitors and biologics (JAKi/biologics) are cornerstone treatments for rheumatoid arthritis (RA). <h3>Objectives</h3> We evaluated the risks of cancers and cardiovascular diseases (CVDs) in patients with seropositive RA (SPRA) treated with JAKi/biologics. <h3>Methods</h3> Patients with new-onset SPRA during 2010–2020 in the national healthcare database were identified. Events of overall and site-specific cancers, as well as CVD outcomes, including deep vein thrombosis, pulmonary embolism, and composite cardiovascular events, were investigated. The relative risk of cancers and CVDs according to treatment was compared by evaluating the incidence rate ratios (IRRs). Time-dependent Cox analyses were performed to evaluate the relationship between JAKi/biologics usage and patient outcomes. <h3>Results</h3> A total of 101,816 and 96,220 patients with SPRA were analyzed for cancers and CVD outcomes, respectively. Compared with patients treated only with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), the IRRs of overall cancers and CVDs in patients administered JAKi/biologics were 0.88 (95% confidence interval [CI] 0.86–0.89) and 0.91 (95% CI 0.90–0.92), respectively. Site-specific lung, liver, prostate, and skin cancers were more frequent in JAKi/biologics users; JAKi did not confer a greater risk of overall CVDs and cancers compared with other biologics and csDMARDs. JAKi/biologics usage was not accounted for overall cancers and CVDs in adjusted Cox analyses. <h3>Conclusion</h3> The incidence of overall cancer and CVD were not increased in patients with SPRA treated with JAKi/biologics and was relatively lower than csDMARDs only users, underscoring optimal disease control for risk mitigation. The higher incidence of several sitespecific cancers requires further investigation. <h3>References</h3> [1] Aletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. Jama 2018;320(13):1360-72. [2] Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79(6):685-99. [3] Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2021;73(7):1108-23. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0005 IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS, MUSCLE-RESTRICTED TCR CLONES SHARE STRUCTURAL FEATURES, WHILE THEIR EXPANSION CORRELATES WITH DISEASE ACTIVITY
Authors: D. Anang, H. Walter, G. Balzaretti, J. Lim, A. Olivieri, L. Van der Weele, I. Niewold, E. Aronica, F. Eftimov, J. Raaphorst, B. Van Schaik, A. Van Kampen, A. J. Van der Kooi, N. De Vries
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> T cells of different lineages including cytotoxic T cells have been implicated in the pathogenesis of idiopathic inflammatory myopathies [1]. However, the question of whether the T cell response in muscle is reflective of the peripheral blood response remains to be fully answered. <h3>Objectives</h3> To characterize the T cell receptor (TCRβ) repertoire in peripheral blood and muscle tissues of treatment naïve patients with newly diagnosed idiopathic inflammatory myopathies (IIMs). <h3>Methods</h3> High throughput RNA sequencing of the TCRβ chain was performed in peripheral blood and muscle tissue in twenty newly-diagnosed treatment-naïve IIM patients and healthy controls. Results thereof were correlated with markers of disease activity. <h3>Results</h3> Muscle tissue of IIM patients show more expansion of TCRβ clones and decreased diversity when compared to peripheral of IIM as well as healthy controls (both p=0.0001). Several expanded TCRβ clones in muscle tissue are tissue restricted and cannot be retrieved in peripheral blood. These clones have significantly longer CDR3 regions when compared to clones (also) found in circulation (p=0.0002), while their CDR3 region is more hydrophobic (p&lt;0.01). Network analysis shows that clonal TCR signatures are shared between patients. Increased clonal expansion in muscle tissue is significantly correlated with increased CK levels (p=0.03), and tends to correlate with decreased muscle strength (p=0.08). <h3>Conclusion</h3> Network analysis of clones in muscle of IIM patients shows shared clusters of sequences across patients. Muscle-restricted TCRβ clones show specific structural features in their T cell receptor, and clonal TCR expansion in muscle tissue is associated with disease activity. These findings indicate that specific clonal T cell responses in muscle tissue act as key players in the pathogenesis of IIM. <h3>Reference</h3> [1]Mizuno, K., et al., Oligoclonal expansion of circulating and tissue-infiltrating CD8+ T cells with killer/effector phenotypes in juvenile dermatomyositis syndrome. Clin Exp Immunol, 2004. <b>137</b>(1): p. 187-94 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
OP0262 INCREASED FERTILITY AMONG 10865 MEN WITH CHRONIC INFLAMMATORY JOINT DISEASES IN NORWAY
Authors: G. D. Sigmo, S. Hauge, K. O. Hufthammer, M. Wallenius, G. Bakland, K. Å. Salvesen, A. K. Daltveit, B. T. Svanes Fevang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In the field of rheumatology, fertility has been reported impaired in Norwegian women with inflammatory joint diseases (IJDs) [1]. There is, however, limited data regarding fertility in male patients. The iFAME-fertility study found an association between inflammatory arthritis and reduced male fertility [2], underlining the need for a large-scale study. In the current project, we address this knowledge gap. <h3>Objectives</h3> To examine whether inflammatory joint diseases (IJDs) have an impact on men's fertility, measured as number of children per man and proportion of childless men. <h3>Methods</h3> We performed a nation-wide, population-based cohort study. Male patients with IJDs (<i>n</i> = 10,865) collected from the Norwegian Arthritis Registry in 2021 were individually matched 1:5 on birth year, sex, and county of residence, with individuals without IJDs obtained from the National Population Register (<i>n</i> = 54,325). Data regarding births was obtained from the Medical Birth Registry of Norway. We compared the mean number of children per man in the patient group and in the comparison group using paired <i>t</i>-tests, and the proportion of childless men using Cochran–Mantel–Haenszel chi-squared tests. <h3>Results</h3> The mean number of children per man in the patient group was 1.80 versus 1.69 in the comparison group (<i>p</i> &lt; 0.001). Altogether, 21% of our patients were childless vs 27% in the comparison group (<i>p</i> &lt; 0.001, Figure 1). The difference in number of children between patients and comparison group was highest for those diagnosed after year 2000 and these patients had the comparatively lowest risk of being childless. The differences were less evident for those diagnosed before 2000 (Table 1). Age at diagnosis did not influence fertility (Table 1). <h3>Conclusion</h3> In this large nationwide study, fertility in male patients with IJDs was not reduced compared to controls, neither when examining the number of children per man, nor when looking at the proportion of childless men. Interestingly, we observed a higher fertility rate in male IJD patients than in the comparison group for patients diagnosed after year 2000. The reason for this observation is unknown. Factors associated with getting or having an IJD may influence fertility. An interesting hypothesis is a possible positive impact of new immune modulating drugs introduced after year 2000. <h3>References</h3> [1]Wallenius M, et al. Fertility in women with chronic inflammatory arthritides. Rheumatology (Oxford). 2011;50(6):1162-7. [2]Perez-Garcia LF, et al. Impaired fertility in men diagnosed with inflammatory arthritis: iFAME-Fertility. Ann Rheum Dis. 2021;80(12):1545-52. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
OP0303-PARE MULTI-STAKEHOLDER CO-CREATION TO FACILITATE CLINICAL TRIAL RECRUITMENT - A FEASIBILITY STUDY
Authors: M. Silva, N. Caeyers
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Recruitment for clinical trials remains a hurdle, causing potential delays in bringing innovative treatments to patients. Furthermore, there is not much communication about clinical trials towards the patient population and the general population has a lot of misconceptions around clinical trials. Communication about clinical trials is also subjected to a strict regulatory framework, especially in Europe. The information that can be found online is often in English and difficult to understand for the lay public. <h3>Objectives</h3> For this reason, a feasibility study has been performed to develop a clinical trial portal for Belgium that allows users to search for trials in a local and lay language, while offering the portal to patient organisations and hospitals to receive updates on newly initiated trials. <h3>Methods</h3> During the feasibility study the following aspects have been analysed by organising multi-stakeholder workshops, involving patient representatives and patient organisations (20), hospitals (8), HCPs (14), industry and representatives (10) of the Belgian medicines agency:user expectations, technical considerations, legal restrictions, regulatory and compliance aspects. Based on the multi-stakeholder workshops, a prototype has been developed that has been tested via user validation workshops. For the field of rheumatology, ReumaNet has represented the RMD community. <h3>Results</h3> The result of the feasibility study revealed that only 15% of patient organisations (out of 190) mention clinical trials on their website, out of 140 websites of hospitals, only 16% mention clinical trials, while 2% have a search engine to search for ongoing studies. All academic hospitals (7) had a section dedicated to trials on their website. There was a great interest from the patient community (over 20 PAG participants) and the HCP representatives. A legal analysis has also set a framework for compliant communication about clinical trials to the lay public as well as a GDPR framework to define privacy related aspects of the portal.The portal has been launched in September 2022 as a first version, an improved version with a PAG dashboard is launched in February 2023. <h3>Conclusion</h3> Based on the feasibility study, a clear need was identified to further develop the clinical trial portal in co-creation with the various stakeholders. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Mitchell Silva Speakers bureau: Paid as a speaker in various pharmaceutical companies to give presentations about patient engagement. These include: AstraZeneca, Boehringer Ingelheim, Roche and MSD., Consultant of: Paid as a consultant to provide input on patient engagement strategy for various companies, including Roche, AstraZeneca, MSD, Janssen, GSK, Takeda, Boehringer Ingelheim, Merck, Nele Caeyers: None declared.
OP0206 PEPTONIPHILUS GORBACHII ALLEVIATES COLLAGEN-INDUCED ARTHRITIS IN MICE BY IMPROVING INTESTINAL HOMEOSTASIS AND IMMUNE REGULATION
Authors: S. Kim, S. H. Chun, S. T. Hong, Y. H. Cheon, M. Kim, H. Lee, H. O. Kim, S. I. Lee, Y. S. Suh
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Although the link between gut microbiota and rheumatoid arthritis (RA) pathogenesis is well established, there is still a lack of information regarding the species-level analysis of microbiota. Recently, studies analyzed blood samples, rather than stool samples, to identify disease-related microbiota at the species level. <h3>Objectives</h3> This study aimed to identify RA-related microbiomes at the species level using serum samples from patients with RA and explore the efficacy as well as mechanisms of candidate microbial species for RA treatment using collegen induced arthritis (CIA) mouse model. <h3>Methods</h3> Serum antibody microarray for 384 microbial species was performed from RA patients (n=81) and healthy control (n=50). We verified the therapeutic effect and mechanism of the candidate microbial species by evaluating arthritis severity, immune response, intestinal barrier integrity, and fecal microbiota using CIA mice. <h3>Results</h3> We discovered 36 altered microbial species in patients with RA compared to healthy controls. In particular, <i>Peptoniphilus gorbachii</i> (PG) was increased in RA patients, inversely correlated with RA disease activity, and competed with <i>Porphyromonas gingivalis</i> which developed and exacerbated RA. Administration of PG suppressed joint inflammation and bone destruction in CIA mice. PG decreases inflammatory T cells and monocytes in the mesenteric and inguinal lymph nodes. Moreover, PG supplementation restored intestinal barrier integrity, with a decreased level of serum zonulin and increased expression of intestinal tight junction proteins. The abundance of fecal microbiota in PG-treated mice correlated with improved intestinal barrier integrity and decreased inflammatory reactions. <h3>Conclusion</h3> Serum microbial antibody microarray could help with the effective discovery of therapeutic microbial RA targets at the species level. Our results suggest that PG exerts a therapeutic effect by restoring intestinal barrier integrity and suppressing the RA-characteristic immunologic response. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
OP0170 INTEROSSEOUS TENDON INFLAMMATION ACROSS THE EARLY ARTHRITIS SPECTRUM: A 10-YEAR MRI-STUDY INVESTIGATING ITS PREVALENCE AT DIAGNOSIS AND RELATION WITH CLINICAL SIGNS
Authors: B. Van Dijk, N. Den Hollander, M. Reijnierse, A. Van der Helm – van Mil
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Inflammation around the tendons of the hand interosseous muscles (interosseous tendon inflammation; ITI) was recently identified on MRI in a set of RA and arthralgia patients. <h3>Objectives</h3> However, the prevalence of ITI at diagnosis of RA is unknown, as is its prevalence in other arthritides and its relationship with clinical signs. These questions prompted us to perform this large MRI study. <h3>Methods</h3> 1,205 consecutive patients presenting with early arthritis between 2010-2020 underwent contrast-enhanced hand MRI. MRIs were evaluated, blind to clinical data, for ITI lateral of MCP2-5 and for other local inflammation (synovitis/tenosynovitis/osteitis, in line with the RA-MRI-scoring-system (RAMRIS)). ITI-presence at baseline was studied in relation to the diagnosis and clinical characteristics (i.e. joint swelling, and tenderness) using logistic regression and generalised estimating equations. <h3>Results</h3> 36% of early RA patients (n=532) had ITI; this was similar in ACPA-negative(37%) and ACPA-positive RA patients (34%; p=0.53). ITI occurred regularly in RS3PE (60%) and connective tissue diseases (44%), and less frequently in undifferentiated arthritis (UA;14%), psoriatic arthritis (14%), inflammatory osteoarthritis (8%), reactive arthritis (7%), crystal arthritis (7%) and peripheral spondyloarthritis (4%). ITI occurred more often in diagnoses with frequent arthritis of the hands (p&lt;0.001) and increased acute-phase-reactants (p&lt;0.001). Within RA, ITI occurred together with local MCP synovitis (OR 2.4 (95%CI; 1.7-3.4)), tenosynovitis (2.4 (1.8-3.3)) and osteitis (2.2 (1.6-3.1)) on MRI. Moreover, ITI-presence associated with local MCP tenderness (1.6 (1.2-2.1)) and swelling (1.8 (1.3-2.6)), independent of age and MRI-detected synovitis/tenosynovitis/osteitis. <h3>Conclusion</h3> ITI occurs regularly in RA and other arthritides with preferential involvement of hand-joints and increased acute-phase-reactants. At MCP-level, the presence of ITI associates independently with joint-tenderness and -swelling. Hence, ITI is a newly identified inflamed tissue mainly found in arthritides with particularly extensive and symptomatic inflammation. <h3>Acknowledgements</h3> W. Nieuwenhuis, E. Newsum, D. Boeters, A. Boer, N. Sidhu and F. Wouters are acknowledged for -scoring MRI-scans. The source image for Figure 1A&amp;B was derived from the digital book 'Anatomy and Physiology' published by OpenStax under a CC BY 4.0 License allowing re-use and adaptation on condition of attribution. The source image was edited. Access for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction. G. Kracht is acknowledged for his help preparing the MRI figure. <h3>Disclosure of Interests</h3> None Declared.
OP0174 CHEST RADIOGRAPHS PRE-IMMMUNOSUPPRESSION HELP TO IDENTIFY NON TUBERCULOUS INFECTIONS AND INTERSTITIAL LUNG DISEASES, BUT ADD LITTLE TO LATENT TUBERCULOSIS SCREENING
Authors: R. Harrington, I. Khan, M. Ramakrishnan, F. Fitzpatrick, L. Durcan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Screening for latent tuberculosis (LTB) using chest x-ray (CXR) and interferon-gamma release assay (IGRA) is standard in patients starting on biologic and immunosuppressive therapies. Our hypothesis is that the CXR does not change management, and we sought to evaluate the additive value of plain radiographs for this purpose in our patients. <h3>Objectives</h3> To retrospectively review all CXRs performed at baseline pre treatment to determine if they provide any additive benefit value to the IGRA LTB screening approach. <h3>Methods</h3> This is a retrospective review of screening practices for LTB in a tertiary referral centre in Ireland, a low prevalence country. We included, 814 patients screened, using CXR and interferon gold release assay (IGRA) over a 5-year period. <h3>Results</h3> The IGRA was positive in 5% (38/814) and indeterminate in 2.5% (20/814), the remainder testing negative. In the IGRA positive group, 15.8% (6/38) had an abnormal CXR. None of these showed changes reflecting prior or active tuberculosis. These showed fibrotic lung disease, consolidations and basal atelectasis. Of those who had an indeterminate IGRA, 45% (9/20) of cases had an abnormal CXR, with one individual report of radiographic evidence of possible prior TB. In those with an abnormal IGRA (positive or indeterminate), the addition of CXR in the screening process changed management in one patient. They were treated for LTBI on the basis of indeterminate IGRA, prior TB contacts, country of origin and other risk factors. The sensitivity of the IGRA alone screening approach was 97.62% when high risk indeterminate results were assumed to have LTB and were treated. The resulting specificity of the IGRA alone approach was 97.80%. The sensitivity of the combined IGRA &amp; subsequent CXR approach was 100% as it was deemed to have captured all actual cases of LTB disease. We acknowledge that this not recognise that IGRA is an imperfect test and assumes that there were no cases of LTB in 756 IGRA negative patients. The specificity of the combined IGRA and subsequent CXR approach remains practically the same at 97.93%. <h3>Conclusion</h3> In conclusion, the clinical utility of the CXR in screening for TB is unclear in this population. The addition of CXR in the screening process only changed management in 1 patient over a 5 year period in this cohort. The incidental identification of interstitial lung diseases and chest infections is of value to patients considering immunosuppression, but is a separate issue to screening for LTB. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.